Reproductive senescence in the female rhesus (18-22 years old) was monitored by analysis of serum estrogen (E), progesterone (P) and LH. While many animals had normal menstrual cycles, a subpopulation displayed irregular cycles or were acyclic with low E and P with elevated LH. This corroborates suggestions that menopause occurs in the mid-twenties. Although the macaque hippocampus is believed to be regulated by ovarian steroids, previous studies failed to detect estrogen receptors (ER-?). To see if the ? form of ER is present in this region, macaque cDNAs for ER-? were isolated and used for ISH. High levels of ER-? were indeed found throughout the monkey hippocampus. Ovarian steroid effects were also detected in the prefrontal cortex. ICC analyses showed an increase of dopamine beta hydroxylase (DBH) and serotonin upon ovariectomy. Immunoreactivity for choline acetyl transferase was unchanged. Replacement with E reversed the effects of ovx on DBH whereas E +P decrea sed serotonin fiber density. In vivo brain imaging was performed using Magnetic Resonance Imaging (MRI) to examine structural changes in aged male monkeys. Image analysis confirmed an age-related increase in the total lateral ventricular volume in a subpopulation of aged animals. The increase in ventricular volume may be predictive of age-related behavioral deficits. The initial phase of participation in the NIA Biomarkers of Aging database has shown that longitudinal changes in animals from this Center, in general, agree with compiled data from other participating Centers. Expansion of this effort is currently being discussed. The establishment of reliable Biomarkers of Aging, such as some blood chemistry values, will be valuable for establishing normative ranges for aged monkeys. This database will also be useful for evaluating the acute effects of experimental manipulations thought to influence the rate of aging and lifespan. FUNDING Nonfederal institutional funds PUBLICATIONS Kohama, SG, Rodrigues SM, Pau C, Urbanski HF. Age-related change of glutamate receptors and neuropathology in the monkey prefrontal cortex. Soc Neurosci Abstr 24:464, 1998 (abstract 179.22).